The Liverpool-born star of Killing Eve, 27, will appear in the blockbuster alongside Matt Damon, Adam Driver and Ben Affleck.
Comer admitted to being torn after finishing shooting in Ireland.
“Such mixed emotions….” she wrote on Instagram.
“Ecstatic to have finished this movie given the circumstances, yet beyond sad to say goodbye to the most wonderful people.”
Comer added: “Thank you so much to the entire cast and crew.”
Comer had been pictured on set wearing a mask alongside her period-appropriate outfit as a coronavirus safety protocol.
The Last Duel is set in 14th Century France. Affleck plays King Charles VI while Damon stars as knight Jean de Carrouges, who is ordered to settle his dispute with his squire (Driver) by challenging him to a duel.
Comer plays Damon’s wife, Marguerite de Carrouges.
The film’s script was penned by Damon and Affleck, who previously won an Oscar for their Good Will Hunting screenplay.
The Last Duel was originally set to be released in December before the pandemic upended the Hollywood release calendar.
It is now set to arrive in October 2021.